Prostate Cancer

In men, the most diagnosed cancer after skin-cancer is prostate cancer, which in most cases arises in luminal or basal epithelial cells of the prostate gland. Prostate cancers often grow slowly and may thus require minimal or no treatment (surveillance), however, a subset may progress quickly into locally advanced and/or metastatic disease. As most prostate cancers rely on androgen signaling, androgen deprivation therapy (ADT) by chemical castration is standard of care for patients that recur after prostatectomy or radiation therapy. However, patients treated with ADT eventually develop resistance (castration-resistant prostate cancer, CRPC), which usually results in progression to a lethal stage. Current focuses in prostate cancer research are first, a better classification between the low-risk and high-risk subtypes, as many (elderly) prostate cancer patients may be over-treated, leading to treatment-induced adverse effects although the disease may have never progressed into a harm-causing malignancy. A second focus is the biology of CRPC. In contrast to previous dogmas, it became clear over the last decade that many CRPC depend on androgen receptor (AR) signaling, and several approaches that inhibit AR signaling (either by blocking de novo steroidogenesis or AR nuclear localization) are now approved to treat patients with metastatic CRPC. However, even these second-generation targeted therapies are accompanied by primary or secondary resistance, which remains a challenge in the clinical management of CRPC. Many resistance mechanisms have been reported that involve genetic, epigenetic and signaling mechanism and lead to restoration or bypass of androgen receptor signaling. In some instances, CRPC become independent of AR signaling, and these tumors show histological signs of neuroendocrine, small cell prostate cancers, which are, compared to adenocarcinomas, rare forms of prostate cancers. The emergence of these neuroendocrine tumors under AR-depletion suggests that prostate adenocarcinomas transdifferentiate into AR-independent tumors as a means to escape selective pressure. Mechanisms that underlie this plasticity are largely unresolved and current focus of prostate cancer research.

TICC Faculty who are involved in Prostate cancer research:

Aaron Ciechanover

Arie Admon

Dina Ron

Gad Rennert

Hossam Haick

Marcelle Machluf

Nathan Karin

Ofer Ben Izhak

Ofer Nativ

Ora Israel

Ron Epelbaum

Tomer Shlomi

Yehuda G. Assaraf

Yuval Shaked

Ze’ev Ronai

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